EP2100596A2 - Formule du paracetamol liquide injectable - Google Patents

Formule du paracetamol liquide injectable Download PDF

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Publication number
EP2100596A2
EP2100596A2 EP09161268A EP09161268A EP2100596A2 EP 2100596 A2 EP2100596 A2 EP 2100596A2 EP 09161268 A EP09161268 A EP 09161268A EP 09161268 A EP09161268 A EP 09161268A EP 2100596 A2 EP2100596 A2 EP 2100596A2
Authority
EP
European Patent Office
Prior art keywords
solution
paracetamol
aqueous
concentration
impurities
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP09161268A
Other languages
German (de)
English (en)
Other versions
EP2100596A3 (fr
Inventor
Faustino Huertas Muñoz
Raúl Fernández Plágaro
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Genfarma Laboratorio SL
Original Assignee
Genfarma Laboratorio SL
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38474429&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP2100596(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Genfarma Laboratorio SL filed Critical Genfarma Laboratorio SL
Publication of EP2100596A2 publication Critical patent/EP2100596A2/fr
Publication of EP2100596A3 publication Critical patent/EP2100596A3/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to an injectable liquid paracetamol composition according to the preamble of claim 1.
  • Paracetamol n-acetyl-4-aminophenol
  • Paracetamol is an active ingredient that has been widely used in the last four decades in pharmaceutical preparations due to its activity as an analgesic and an antipyretic which was introduced by Von Mering in 1893. It is further well tolerated by human beings and does not alter the acid-base equilibrium, therefore it is widely used to relive pain both in adults and in children and in the elderly.
  • a large number of pharmaceutical preparations to be administered orally or even topically are known.
  • the secondary cause of degradation may be the deacetylation of the amino group generating p-aminophenol which is also quickly degraded producing p-benzoquinoneimine. This deacetylation takes places both at acid pH and (much faster) at basic pH once the phenolate form is present.
  • FR-A1-2 751 875 discloses aqueous paracetamol solutions for use in perfusion with a pH between 5 and 7.
  • the pH value is maintained by using a buffer system comprising an acid and an alkali metal of acetates or phosphates. It further comprises stabilizing substantes such as derivatives of sulphurous acid group, e.g. formaldehyde sulfoxylate.
  • the problem to be solved by the present invention is to provide an alternative stable injectable paracetamol solution preventing the development of an unwanted color of the solution over time.
  • aqueous paracetamol solutions for their use by perfusion of the invention comprise a substance that can react with phenolates turning them into their O-derivatives or coordination compounds.
  • such agents are selected from the group consisting of reducing sugars such as glucose, galactose, fructose; the acid forms of these sugars or their salts, such as gluconate, glucuronate, glucoheptanoate, galactate; chemical species containing sulfur in an oxidation state less than +6, sodium formaldehyde sulfoxylate, sulfites or thiourea or any combination of the previous substances.
  • These compositions produce a solution with very reduced levels of impurities and the absence of color in the solution for long time periods, being able to be stored in antioxidant-free plastic materials.
  • this is achieved by adding at least one stabilizing substance of paracetamol in solution selected from the group consisting of glucose, fructose, or gluconate in a concentration between 0.4% m/v - 3.3% m/v and sodium formaldehyde sulfoxylate, sodium sulfite or sodium dithionite in a concentration between 0.0008% - 0.02% m/v.
  • the addition of the cited stabilizing substances is not intended to provide isotonicity to the solutions of the invention, and moreover it would be insufficient for that purpose.
  • solubility of paracetamol in aqueous medium is of the order of 12 mg/ml at a temperature of 20°C and 8 mg/ml at 4°C, such that the process or composition of the solution must prevent the crystallization of paracetamol.
  • This effect is solved by means of filtering the solution through a pore size of 0.45 microns or less, or adding a solubilizing agent as described in international publication WO003033026 issued to BIOREN S.A., disclosing an aqueous paracetamol solution obtained by mixing paracetamol and propylene glycol in citrate medium at a pH comprised between 4.5 and 6.5 and heating said solution at a temperature between 70°C-130°C.
  • solutions with a variable composition have been made all in presence of oxygen, without a previous deoxygenation of the solvent media, and stored in glass and PVC (poly(vinyl chloride)) materials to later subject them to wet heat sterilization, which is the safest currently admitted process for injectable solutions.
  • PVC poly(vinyl chloride)
  • the stability of the solution in room temperature conditions of product storage can be predicted by means of observing the characteristics of the solutions subjected to these heat treatments at different times, because, as indicated by K. Thomas Koshy, the degradation kinetics follow the Arrhenius law depending on temperature/time.
  • the three characteristics studied, visual appearance, absorbance at different wavelengths and content of impurities, are related to one another.
  • the absorbance at 350 nm (yellow) is caused by p-aminophenol, polymerization products, impurities related to the synthesis of paracetamol and benzoquinoneimines;
  • the absorbance at 500 nm (pinkish brown) is caused by benzoquinoneimines and their polymerization.
  • Table 1 indicates the maximum values for the impurity corresponding to the area of the chromatographic peak with the highest value, expressed as % with respect to paracetamol. The sum of all the impurities is indicated as a % total impurity value.
  • the solution containing dithionite, glucose or sodium formaldehyde sulfoxylate are the ones with less color, showing values of absorbance at 350 nm that are less than 0.100 absorbance units and at 500 nm less than 0.020 absorbance units.
  • the formulation containing oxygen in the aqueous media and sodium sulfoxylate at a concentration of 0.02% m/V can equal the stability of the commercial formulation Perfalgan ® (obtained according to the process described in the SCR Pharmatop patent), which formulation, kept in its original glass bottle for 24 hours at 100°C, remains colorless with virtually nil absorbances at 350 nm and 500 nm.
  • the studied compositions have a much higher stability than that of Perfalgan ® when it is stored in plastic material.
  • the Perfalgan ® solution in PVC thus has an intense grayish brown color after it is kept for 67 hours at 70°C with an absorbance of 0.267 AU at 350 nm and of 0.38 AU at 500 nm.
  • the concentration of antioxidant has an important role in the stabilization of the solution because the degradation of such antioxidant in turn generates impurities providing color to the solution.
  • sugars they can produce other furfurals and gluconated derivatives, in the case of reducing substances with sulfur, they can produce sulfonated derivatives of paracetamol which can in turn also provide color to the solution, or the inorganic form of sulfates.
  • the formulations comprises at least one stabilizing substance of paracetamol in solution which is glucose in a concentration between 0.4% and 3.3% m/v; in a more preferred embodiment of the invention, the formulation comprises glucose in a concentration between 0.5% and 3.0% m/v; in the most preferred embodiment of the invention, the formulation comprises glucose in a concentration between 1.0% and 3.0%.
  • the formulations of the inventions comprises sodium formaldehyde sulfoxylate in a concentration between 0.008% and 0.02%; in a more preferred embodiment of the invention, the formulation comprises sodium formaldehyde sulfoxylate in a concentration between 0.001% and 0.02%.
  • antioxidant substances that can react with p-aminophenolates giving rise to their O-derivatives or coordination compounds, preferably selected from the group consisting of reducing sugars such as glucose, galactose, fructose; acid forms of the sugars or their salts such as lactobionate, gluconate; glucuronate; glucoheptanoate, galactate, lactobionate or lactones such as gluconolactone; chemical species containing sulfur in an oxidation state less than +6, sodium formaldehyde sulfoxylate, sulfites or thiourea, and it is possible that these substances can produce derivatives with the phenolate form of paracetamol.
  • reducing sugars such as glucose, galactose, fructose
  • acid forms of the sugars or their salts such as lactobionate, gluconate; glucuronate; glucoheptanoate, galactate, lactobionate or lactones such as
  • Injectable paracetamol solutions with a content of impurities that is less than 0.1% can thus be obtained.
  • the solutions of the invention further have the advantage that they can be contained in glass bottles or bottles of any other type of plastic materials including PVC, and they can be sterilized by heat or filtration.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pain & Pain Management (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Detergent Compositions (AREA)
EP09161268A 2006-07-18 2007-07-12 Formule du paracetamol liquide injectable Withdrawn EP2100596A3 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/ES2006/070108 WO2008009756A1 (fr) 2006-07-18 2006-07-18 Formulation liquide injectable de paracétamol
EP07112327A EP1889607B1 (fr) 2006-07-18 2007-07-12 Formule du paracetamol liquide injectable

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP07112327A Division EP1889607B1 (fr) 2006-07-18 2007-07-12 Formule du paracetamol liquide injectable
EP07112327.7 Division 2007-07-12

Publications (2)

Publication Number Publication Date
EP2100596A2 true EP2100596A2 (fr) 2009-09-16
EP2100596A3 EP2100596A3 (fr) 2010-04-28

Family

ID=38474429

Family Applications (2)

Application Number Title Priority Date Filing Date
EP09161268A Withdrawn EP2100596A3 (fr) 2006-07-18 2007-07-12 Formule du paracetamol liquide injectable
EP07112327A Active EP1889607B1 (fr) 2006-07-18 2007-07-12 Formule du paracetamol liquide injectable

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP07112327A Active EP1889607B1 (fr) 2006-07-18 2007-07-12 Formule du paracetamol liquide injectable

Country Status (17)

Country Link
US (2) US9943479B2 (fr)
EP (2) EP2100596A3 (fr)
JP (1) JP4929352B2 (fr)
AT (1) ATE432690T1 (fr)
AU (2) AU2006346318B2 (fr)
CA (1) CA2628806C (fr)
CY (1) CY1110480T1 (fr)
DE (1) DE602007001215D1 (fr)
DK (1) DK1889607T3 (fr)
ES (1) ES2327286T3 (fr)
HR (1) HRP20090350T1 (fr)
MA (1) MA31346B1 (fr)
PL (1) PL1889607T3 (fr)
PT (1) PT1889607E (fr)
RU (1) RU2419421C2 (fr)
SI (1) SI1889607T1 (fr)
WO (1) WO2008009756A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014083071A1 (fr) * 2012-11-27 2014-06-05 Genfarma Laboratorio, S.L. Préparation liquide injectable consistant en une combinaison de tramadol et de paracétamol

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2926992B1 (fr) * 2008-02-06 2011-01-14 Moly Pharma Formulation d'une solution de paracetamol injectable,procede de preparation et de conditionnement d'une telle solution et dispositif de conditionnement d'une telle solution
EP2243477A1 (fr) 2009-04-22 2010-10-27 Fresenius Kabi Deutschland GmbH Paracétamol destiné à l'administration parentérale
US8404748B2 (en) 2009-08-13 2013-03-26 Neogen N.V. Storage-stable formulation of paracetamol in aqueous solution
JP5845193B2 (ja) * 2010-01-21 2016-01-20 アプレア エイビー 過増殖性疾患、自己免疫疾患、および心疾患の治療のための３−キヌクリジノンを含有する水溶液
EP2377516B1 (fr) 2010-04-14 2012-06-20 B. Braun Melsungen AG Composition de paracétamol
ES2414557B1 (es) 2012-01-16 2014-06-10 Novocat Farma, S.A. Composición acuosa de paracetamol para inyección
ITMI20121154A1 (it) * 2012-06-29 2013-12-30 Sint Sa Soluzione iniettabile di acetaminofene per la somministrazione spinale
US20140303254A1 (en) * 2013-04-08 2014-10-09 InnoPharma Licensing LLC Process Of Manufacturing A Stable, Ready To Use Infusion Bag For An Oxidation Sensitive Formulation
BR102014005885B1 (pt) * 2014-03-13 2021-04-13 Biotec Biológica Indústria Farmacêutica Ltda E.P.P Formulação farmacêutica líquida injetável estável de paracetamol em bolsa plástica pronta para uso
EP3171868B1 (fr) * 2014-07-25 2020-09-30 Terumo Kabushiki Kaisha Préparation de solution pour injection d'acétaminophène conditionnée
JP2019506407A (ja) * 2016-02-05 2019-03-07 イノファーマ インク 酸化感受性製剤のための安定なすぐ使用できる注入バッグを製造するプロセス

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003033026A1 (fr) 2001-10-16 2003-04-24 Bioren S.A. Solutions injectables a base de paracetamol pretes a l'emploi, contenant du propylene glycol utilise comme unique cosolvant
EP0858329B1 (fr) 1996-08-05 2003-06-04 SCR Pharmatop Nouvelles formulations liquides stables a base de paracetamol et leur mode de preparation
WO2004071502A1 (fr) 2003-02-14 2004-08-26 Tho Nguyen-Xuan Formulation liquide injectable de paracetamol

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4440815A (en) 1981-06-29 1984-04-03 Abbott Laboratories Clear, autoclavable plastic formulation for medical liquid containers
KR100226191B1 (ko) 1997-04-03 1999-10-15 구광시 음료용 플라스틱 병
WO1999021442A1 (fr) * 1997-10-23 1999-05-06 Morinaga Milk Industry Co., Ltd. Procede et dispositif permettant de steriliser thermiquement en continu un liquide
DE69736140T2 (de) * 1997-11-18 2007-04-19 Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A. Pharmazeutische injizierbare Lösungen, die Paracetamol und Kombinationen aus Paracetamol mit anderen Aktivsubstanzen enthalten
IT1301976B1 (it) 1998-07-31 2000-07-20 Angelini Ricerche Spa Composizione farmaceutica iniettabile a base di paracetamolo
FR2809619B1 (fr) * 2000-06-06 2004-09-24 Pharmatop Nouvelles formulations aqueuses de principes actifs sensibles a l'oxydation et leur procede d'obtention
DE10112325A1 (de) 2001-03-13 2002-10-02 Fresenius Kabi De Gmbh Lagerstabile Fertiginfusionslösungen des Paracetamols
US20050203175A1 (en) 2001-12-18 2005-09-15 Ioulia Tseti Parenteral composition of paracetamol
DE60315020T2 (de) 2002-05-27 2008-04-17 Kyorin Pharmaceutical Co., Ltd. (2s)-2-ethylphenylpropionsäurederivat
AU2003251152A1 (en) 2002-07-03 2004-01-23 Shannon Biotechnology Ltd Pharmaceutical formulations for preparing drink products
FR2862872A1 (fr) 2003-12-02 2005-06-03 Palbian Snc Composition a l'etat aqueux pour l'application perfusable d'un principe actif, notamment pharmacologique tel que le paracetamol.
US20060292225A1 (en) 2005-06-24 2006-12-28 Felix Arthur M Water soluble analgesic formulations and methods for production

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0858329B1 (fr) 1996-08-05 2003-06-04 SCR Pharmatop Nouvelles formulations liquides stables a base de paracetamol et leur mode de preparation
ES2201316T3 (es) 1996-08-05 2004-03-16 Scr Pharmatop Nuevas formulaciones liquidas estables a base de paracetamol y su modo de preparacion.
WO2003033026A1 (fr) 2001-10-16 2003-04-24 Bioren S.A. Solutions injectables a base de paracetamol pretes a l'emploi, contenant du propylene glycol utilise comme unique cosolvant
WO2004071502A1 (fr) 2003-02-14 2004-08-26 Tho Nguyen-Xuan Formulation liquide injectable de paracetamol

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
K. THOMAS KOSHY; JON L. LACH: "Stability of aqueous solutions of N-acetyl-p-aminophenol", J. OF PHAR. SCI., vol. 50, no. 2, 1961, pages 113 - 118
K.T. KOSHY; J.L. LACH: "Stability of aqueous solutions of N-acetyl-p-aminophenol", J. PHARMACEUTICAL SCIENCES, vol. 50, no. 2, February 1961 (1961-02-01), pages 113 - 118

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014083071A1 (fr) * 2012-11-27 2014-06-05 Genfarma Laboratorio, S.L. Préparation liquide injectable consistant en une combinaison de tramadol et de paracétamol

Also Published As

Publication number Publication date
PL1889607T3 (pl) 2009-10-30
AU2006346318B2 (en) 2011-02-10
RU2419421C2 (ru) 2011-05-27
PT1889607E (pt) 2009-07-20
CA2628806A1 (fr) 2008-01-24
EP1889607A1 (fr) 2008-02-20
DE602007001215D1 (de) 2009-07-16
JP2009543851A (ja) 2009-12-10
ATE432690T1 (de) 2009-06-15
AU2011201253B2 (en) 2012-03-29
CY1110480T1 (el) 2015-04-29
US20160199325A1 (en) 2016-07-14
SI1889607T1 (sl) 2009-10-31
US9943492B2 (en) 2018-04-17
DK1889607T3 (da) 2009-07-27
AU2011201253A1 (en) 2011-04-07
MA31346B1 (fr) 2010-05-03
HRP20090350T1 (en) 2009-08-31
EP2100596A3 (fr) 2010-04-28
US9943479B2 (en) 2018-04-17
ES2327286T3 (es) 2009-10-27
EP1889607B1 (fr) 2009-06-03
US20090215903A1 (en) 2009-08-27
JP4929352B2 (ja) 2012-05-09
AU2006346318A1 (en) 2008-01-24
CA2628806C (fr) 2012-08-21
WO2008009756A1 (fr) 2008-01-24
RU2009105480A (ru) 2010-08-27

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